ANNULATED PYRANSIDES FOR OPTICALLY ACTIVE POLYQUINANES

光学活性聚喹烷的环状吡喃酯

• 批准号: 3292674
• 负责人: Bertram Oliver Fraser-Reid
• 金额: $ 14.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3292674
• 关键词: anomer; antineoplastic antibiotics; conformation; dental caries inhibitor; drug design /synthesis /production; glycosides; nuclear magnetic resonance spectroscopy

Actinobolin and bactinobolin are congeners that are closely structurally related. However, their biological activities are most dissimilar. Actinobolin was for several years widely investigated, but its prospects as an antibiotic were not encouraging. However, much interest currently centers around its use for oral hygiene in preventing the formation of dental caries. Bactinobolin, on the other hand, is a promising antitumor agent, being up to one-thousand times more potent than actinobolin. Our synthetic plan is to prepare actinobolin in optically active form from a carbohydrate precursor. We intend to take advantage of our observation that in "annulated pyranosides", the anomeric effect operating in the pyranoside moiety, controls the conformation of the entire assembly. Thus stereocontrolled transformations can be carried out on the "annulus". Allied studies will be undertaken to help amplify and clarify qualitative and quantitative aspects of the anomeric effect. These will extend to theoretical studies to be undertaken jointly with Professor Dennis Liotta. Actinobolin is to be synthesized first and minor changes at late stages of the synthetic plan will enable us to achieve bactinobolin. Relay studies from actinobolin itself will influence our synthetic design.

Actinobolin和Bactinobolin是结构上紧密相关的同系物， 相关. 然而，它们的生物学活性是最不同的。 放线菌素被广泛研究了几年，但它的前景， 抗生素并不令人鼓舞。 然而，目前很多人 中心围绕其用于口腔卫生， 龋病 另一方面，Bactinobolin是一种很有前途的抗肿瘤药物， 它比放线菌酮强一千倍。 我们 合成方案是由一种具有光学活性的放线菌酮， 碳水化合物前体 我们打算利用我们的观察 在“环状吡喃糖苷”中， 吡喃糖苷部分控制整个组装体的构象。 因此 立体控制的转化可以在“环”上进行。 联合研究将进行，以帮助扩大和澄清定性 和异头效应的定量方面。 这些将延伸到 与丹尼斯·廖塔教授共同进行理论研究。 Actinobolin首先合成，在合成的后期进行微小的改变。 合成计划将使我们能够获得bactinobolin。 接力研究 会影响我们的合成设计